Biomedical Engineering - Research Publications

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Author: Morokoff, Andrew × Start date: 2020 × End date: 2021 ×

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    Non-Invasive Measurement of Intracranial Pressure Through Application of Venous Ophthalmodynamometry.
    Lo, L ; Zhao, D ; Ayton, L ; Grayden, D ; Bui, B ; Morokoff, A ; John, S (IEEE, 2021-11)
    Non-invasive intracranial pressure (ICP) monitoring is possible using venous ophthalmodynamometry to observe a pulsation in retinal blood vessels when intraocular pressure (IOP) exceeds ICP. Here, we identify features in the eye - optic disc and retinal blood vessel locations - and identify pulsation in large retinal blood vessels. The relationship between force and the magnitude of pulsation is used to estimate ICP when force is applied to the eye to gradually increase IOP over time. This approach yields 77% accuracy in automatically observing vessel pulsation.Clinical Relevance - Non-invasive ICP monitoring is desirable to improve patient outcome by reducing potential trauma and complications associated with invasive assessment with intracranial sensors or lumbar puncture.
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    EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism
    Gomez, J ; Areeb, Z ; Stuart, SF ; Nguyen, HPT ; Paradiso, L ; Zulkifli, A ; Madan, S ; Rajagopal, V ; Montgomery, MK ; Gan, HK ; Scott, AM ; Jones, J ; Kaye, AH ; Morokoff, AP ; Luwor, RB (MDPI, 2021-03)
    Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.
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    Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience
    Oxley, TJ ; Yoo, PE ; Rind, GS ; Ronayne, SM ; Lee, CMS ; Bird, C ; Hampshire, V ; Sharma, RP ; Morokoff, A ; Williams, DL ; MacIsaac, C ; Howard, ME ; Irving, L ; Vrljic, I ; Williams, C ; John, SE ; Weissenborn, F ; Dazenko, M ; Balabanski, AH ; Friedenberg, D ; Burkitt, AN ; Wong, YT ; Drummond, KJ ; Desmond, P ; Weber, D ; Denison, T ; Hochberg, LR ; Mathers, S ; O'Brien, TJ ; May, CN ; Mocco, J ; Grayden, DB ; Campbell, BC ; Mitchell, P ; Opie, NL (BMJ PUBLISHING GROUP, 2021-02)
    BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.